Activation of p38/MEF2C pathway by all-trans retinoic acid in cardiac myoblasts.

Myocyte enhancer factor 2C (MEF2C) is a transcription factor particularly expressed in cardiac muscle. While the effects of all-trans retinoic acid (atRA) on embryonic heart are well described, the mechanism of atRA action on MEF2C activity in cardiomyocytes is less known. The aim of the present study was to investigate whether and how atRA regulates MEF2C activity in H9c2 rat ventricular cells. Here, our results, obtained from Western blot and protein kinase assays, showed that the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and MEF2C was induced by atRA in H9c2 myocardial cells. And the result from luciferase assays showed that the transactivation activity of MEF2C was upregulated by p38. Furthermore, using confocal microscopy and immunoprecipitation, we found that atRA hastened p38 translocation into nuclei to interact with MEF2C, and SB202190 inhibited nuclear translocation of p38. These results suggest that atRA may mediate p38/MEF2C signaling pathway during heart development.